Dimethyl pyridine-2,3-dicarboxylate

Methyl pyridinecarboxylates can be converted to the corresponding amide on treatment with MgCl2 or MgBr2 in the presence of a range of primary and secondary amines <2001TL1843>. The reaction of the dimethyl pyridine-2,3-dicarboxylate with the 2,5-isomer occurs selectively at the 2-position. 

Derivatives of dimethyl pyridine-2,3-dicarboxylate result from the action of dimethyl acetylenedicarboxylate on the dienamines 107 (equation 126)154. 

In contrast to the method given above, the higher reactivity of the ester function allows milder conditions for syntheses of substituted derivatives 6 starting from the appropriate pyridine-2,3-dicarboxylic esters and hydrazines. Earlier examination of this reaction did not emphasize the ease with which such reactions take place, e.g. either room temperature41 or temperatures around 90°C.42-44 TV-Oxides, such as dimethyl pyridine-2,3-dicarboxylate 1-oxide, also undergo a similar reaction with hydrazine.45... 

Pyridonecarboxylic acid esters. F2 (diluted with N2) bubbled into a soln. of dimethyl pyridine-2,3-dicarboxylate in 2 1 acetonitrile/water for 20 min at 0 , flushed with N2 for 30 min at room temp., and refluxed for 2 h-+ dimethyl 1,6-dihydro-6-oxopyridine-2,3-dicarboxylate. Y 56%. F.e. inch oxidation of 2-, 3- and 4-carboxypyridines, and of methyl quinoline-4-carboxylate, s. M. Van Der Puy et al.. Tetrahedron Letters 29, 4389-92 (1988). 

Ethanol added to Na-wire, then dimethyl pyridine-2,3-dicarboxylate and diethyl succinate, both with dry xylene, added simultaneously and dropwise to the vigorously stirred mixture, stirring and refluxing continued 1.5 hrs. diethyl 5,8-dihydroxyquinoline-6,7-dicarboxylate. Y 58%. F. e. s. G. and R. K. Jones, Soc. Perkin I 1973, 26. 

A good example of template copolycondensation has been described by Ogata et al Copolycondensation of 2,6-dimethyl pyridine dicarboxylate and dimethyl adipate with hexamethylene diamine was carried out in the presence of polysaccharide - Pullulane (mol. weight 30,000) used as a template. The reaction was carried out in DMSO at 60 C. It was found that the content of 2,6-dimethyl pyridine dicarboxylate units in the copolyamide, determined by NMR analysis, increased in the presence of Pullulane in comparison with the amount obtained in the absence of the template. This effect can be explained by preferential adsorption by the template of monomer having pyridine groups in comparison with the adsorption of dimethyl adipate. A set of experiments was carried out under the same conditions, but in the presence of poly(acrylonitrile) instead of Pullulane. The composition of copolyamides was the same as in copolycondensation without the template. 

To a solution of methyl 3-oxobutanoate 127 (580 mg, 5 mmol) and l-methyl-2-methylthio-l//-imidazole-5-carboxaldehye 128 (390 mg, 2.5 mmol) in 5 mL of absolute methanol was added a solution of ammonium hydroxide (25%, 0.4 mL). The reaction was heated at reflux overnight before cooling to room temperature and removing the solvent. The crude product was purified by preparative TLC to afford 526 mg of dimethyl l,4-dihydro-2,6-dimethyl-4-(l-methyl-2-methylthio-5-imidazolyl)-3,5-pyridine-dicarboxylate 129 (60%) as a solid, mp = 200-201 °C (MeOH). 

To avoid problems with the separation of regiomers, dimethyl acetylene dicarboxylate (DMAD) was chosen as a dienophile. The intermolecular Diels-Alder reactions were performed in refluxing dichlorobenzene (bp 132 °C), while the intramolecular reaction of alkyne tethered pyrazinone required a solvent with a higher boiling point (bromobenzene, bp 156 °C). In the case of 3-methoxy or 3-phenyl pyrazinones a mixture of pyridinones and pyridines was obtained, while for the alkyne tethered analogue only the di-hydrofuropyridinone was isolated as the single reaction product. 

N-silylated imines 509 react with the Li salts of tosylmethylisonitriles to give 4,5-disubstituted imidazoles in moderate yields [93]. Acetylation of N-trimethylsilyl imines 509 with acetyl chloride and triethylamine affords 72-80% of the aza-dienes 510 these undergo readily Diels-Alder reactions, e.g. with maleic anhydride at 24 °C to give 511 [94] or with dimethyl acetylenedicarboxylate to give dimethyl pyridine-3,4-dicarboxylates [94] (Scheme 5.29). 

Mesoionic 4-amino-l,2,3,5-thiatriazoles constitute the only class of mesoionic 1,2,3,5-thiatriazoles known. They are prepared by the reaction of l-amino-l-methyl-3-phenylguanidine with approximately 2 equivalents of thionyl chloride with pyridine as solvent (88ACS(B)63>. They are obtained as the yellow 1 1 pyridine complexes (17). The dark-violet mesoionic 1,2,3,5-thiatriazole (18) was liberated on treatment with aqueous potassium carbonate (Scheme 3). The structure is established on the basis of elemental analysis and spectroscopic data. In particular, the IR spectrum is devoid of NH absorptions. Compound (18) exhibits a long-wavelength absorption at 463 nm in methanol. When mixed with an equivalent amount of pyridinium chloride, complex (17) is formed and the absorption shifts to 350 mn. The mesoionic thiatriazoles are sensitive towards mineral acids and aqueous base and although reaction takes place with 1,3-dipolarophiles such as dimethyl acetylene-dicarboxylate, a mixture of products were obtained which were not identified. 

Many other compounds are presendy in use a 1993 database search showed 27 active ingredients in 212 products registered by the U.S. EPA for human use as repellents or feeding depressants, including octyl bicycloheptene dicarboxamide (lV-2-ethylhexylbicyclo[2.2.1]-5-hepten-2,3-dicarboxamide), dipropyl isocinchomeronate (2,5-pyridine dicarboxylic acid, dipropyl ester), dimethyl phthalate, oil of citronella, cedarwood oil, pyrethrins, and pine tar oil (2). Repellent—toxicant or biting depressant systems are available which are reasonably comfortable for the user and can protect completely against a number of pests for an extended period of time (2). 

The ultraviolet absorption spectra have been used to distinguish between the tautomers obtained by addition of dimethyl acetylene-dicarboxylate to pyridines. The 4/f-quinolizines show a band around 265 mfi. which is missing from the spectra of the 9a/f-quinolizines. Acheson and Taylor26 have successfully used this information to settle the constitution of the stable and labile adducts obtained by the action of acetylenedicarboxylic esters on pyridines. The ultraviolet spectra of the stable adducts formed by the above methods show... 

Abbreviations arene, i/6-benzene or substituted benzene derivative bipy, 2,2 -bipyridyl Bu, Bu", Bu, iso-, n-, or rerf-butyl COD, 1,5-cyclo-octadiene Cp, /5-C5H5 DAD, dimethyl-acetylene dicarboxylate dam, 1,2-bis(diphenylarsino)methane DBA, dibenzylideneacetone DMF, A. A -dimethylformamide dpe, l,2-bis(diphenylphosphino)ethane dpen, os-l,2-bis(di-phenylphosphino)ethylene dpm, 1,2-bis(diphenylphosphino)methane ESR, electron spin resonance F6-acac, hexafluoroacetylacetone FN, fumaronitrile MA, maleic anhydride Me, methyl MLCT, metal ligand charge transfer phen, 1,10-phenanthroline Pr , Pr", iso- or n-propyl py, pyridine RT, room temperature TCNE, tetracyanoethylene tetraphos, (Ph2PCH2CH2)jP THF, tctrahydrofuran Xylyl, 2,6-Me2C6H3. 

The l,4-dihydro-2,6-dimethyl-4-(2- or 3-nitrophenyl)-3,5-pyridine-dicarboxylate derivatives nifedipine (NF), nitrendipine (NT), and nimodipine (NM) were supplied by Bayer AG (Wuppertal, Germany). Analytical grade reagents were used at all times, toluene AR (Riedel-de-Haen AG, Seelze, Germany) was distilled over a 50 cm Vigreux column before use. Sodium hydroxide, 0.5 mol/L, was purchased from J.T. Baker Chemical Corp. (USA) and the amber screw-cap autosampler bottles (2 mL) were obtained from Pierce Biotechnology Inc. (Rockford IL USA) and rinsed with acetone before use. 

Two-dimensional structures result when pyridine-dicar-boxylic acids are used. The complex trans-VACliLi (L = 2,6-dimethyl pyridine-3,5-dicarboxylic acid) (149) self-assembles to yield a two-dimensional sheet structure that involves hydrogen bonding between the carboxylic acid groups mediated by methanol solvent molecules (Scheme 31). 

DJB460 CAS 23125-28-2 HR 3 DIETHYL 2,6-DIMETHYL-4(2-PYRIDYL)-1,4-DIHYDRO-3,5-PYRIDINE-DICARBOXYLATE... 

Miscellaneous examples of the photoaddition of solvent and other simple molecules to nitrogen-containing systems have been described. Methoxylation, methylation, and hydroxymethylation arising via ionic and radical pathways have been observed on irradiation of dimethyl pyridine-2,4-dicarboxylate in methanol. The photomethoxylation of methyl pyridine-2-carboxylate in acidified methanol is facilitated by added 4-substituted pyridines such as 4-cyanopyridine an excited complex is thought to be involved. 

As expected, 1 and 2 undergo Diels-Alder reactions with dimethyl acetylene-dicarboxylate to give pyridines (from 1) or biphenyl derivatives (from 2). 

Figure U.1D. Nicotinamide analogs tested in pellagra or animal models of pellagra. The active compounds include (1,2, 6, 11, 12, 13,15,18, and 20). Compounds active in some models or in pellagrainclude (7,17,21), pyrazine-2,3-dicarboxylic acid, NAD, pyridyl-3-aldehyde,pyridyl-3-carbi-nol, tryptophan, and 3-hydroxyanthranilicacid. The inactive compounds are (3,4,5,8,9,10,14,16, 19), 3-arninopyridine,thiazole-5-carboxylicacid, 2-methylpyridine, 3-methylpyridine, 2,6-dimethyl-pyridine-3,5-dicarboxylic acid, pyridine-3,5-dicarboxylic acid, kynurenine, 3-hydroxykynurenine, and formylkynurenine. This figure is from Ref 33 and is used with permission.

Hydrazinolysis of dimethyl pyridine-3,4-dicarboxylate gives the hydrazinium salt of a pyridine-3,4-dicarboxylic acid monohydrazide, thought to be the 4-carboxylic acid 1. The hydrazinium salt or free acid, respectively, on heating at 365-370°C cyclizes to give pyrido[3,4-t/]-pyridazine-1,4-(2//,3//)-dione (2).117... 

The synthesis of [2.2.3]cyclazines, aza[2.2.3]cyclazines and their derivatives has also been covered. The attention of the reviewers has been focused on the study of the developments in the synthesis of several benzocyclazines and azacyclazines by the [8 -I- 2] cycloaddition reaction of the dimethyl acetylene dicarboxylate with various types of indolizines. The synthesis of indolizines, imidazo[l, 2-a]pyridines, and related compounds, which are key intermediates for the synthesis of cyclazines, is also described <88H(27)225i>. 

The gas-phase equilibrium between 2-hydroxypyridine and 2-pyridone favours the hydroxy-form, but in the equilibrium between 2-hydroxypyridine iV-oxide and N-hydroxy-2-pyridone, the major tautomer is the hydroxy-pyridone. Bicyclic adducts between 2-pyridones and dimethyl acetylene-dicarboxylate, unobtainable at atmospheric pressure, have been obtained at 10—15 kbar. A novel route to iV-hydroxy-2-pyridone involves the trimethyl-silylation of 2-pyridone followed by oxidation of the resulting 2-(trimethyl-silyloxy)pyridine with the DMF complex of molybdenum pentoxide. p-Nitro-phenols (45) and nitro-acetamides (46) are formed from the reaction of 3,5-dinitro-2-pyridones (43) with the sodium salts of /3-keto-esters (44) (Scheme 20). ... 

The photocycloaddition chemistry of pyridines substituted with electron-donor and electron-acceptor groups at the 2- and 3- positions continues to be exploited. The results of irradiation of such pyridines in the presence of 2-cyanofuran have now been described. The yields of the (47r+47r) cycloadducts (29) and (30), the pyridine dimer (31) and the transposition isomer (32) are dependent on the level of methyl substitution on the heteroarene and are given in Scheme 2. Other photocycloadditions to heteroarenes reported within the year include the reactions of benzodithiophene (33) with butadiyne derivatives and dimethyl acetylene dicarboxylate, giving low yields of (34) and (35) respectively, the latter from photorearrangement of the primary adduct (36). The (271+471) photocycloaddition of indoles (37) to cyclohexa-1,3-dienes (38) is sensitized by the aromatic ketones (39), and yields (14-46%) of the exo and endo isomers of the adduct (40) in ratios which are dependent on the substituents on the addends. 

This reaction was initially reported by Diels and Reese in 1934. It is the conjugate addition between hydroazobenzene and dimethyl acetylene-dicarboxylate. The resulting adduct can be transformed into three different heterocyclic compounds under various experimental conditions (i.e pyrazolones with acid, indoles upon heating in xylene, and quinolones with base ). For example, l,2-diphenyl-3-carbomethoxy-5-pyrazolone will be generated from the adduct in acetic acid (acidic condition), whereas dimethyl indole-2,3-dicarboxylate is produced in xylene (neutral condition) and 2-hydroxy-3-anilino-4-carbomethoxy-quinoline is yielded in pyridine (basic condition). The latter can be further converted into 2,3-dihydroquinoline upon decarboxylation and hydrolysis." This reaction has been extended to heat the 1 1 adduct in picoline. ... 

The above results show that in reactions with arynes, pyrrolinediones act as synthetic equivalents of azadienes. One therefore wonders how they behave in reactions with other dienophiles. Is it possible to generalize the method described above to obtain a new synthetic route to pyridones and pyridines As a step in this direction, we have found that the pyrrolinedione 29b reacts rapidly with dimethyl acetylene dicarboxylate (DMAD) to give the emetine 42 in 75% yield (Scheme 14)(Ref. 21). 

Hydrogenation of dimethyl pyridine-3,4-dicarboxylate (X-177) over palladium-on-charcoal affords the 1,4,5,6-tetrahydro derivative p(-178), which, on further reduction over platinum oxide, yields the piperidine derivative (X-179). On the other hand, dimethyl pyridine-23-dicarboxylate (X-180) is reduced over palladium-on-charcoal directly to the piperidine (X-181)." ... 

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